Transcriptome Analysis of Canine Histiocytic Sarcoma Tumors and Cell Lines Reveals Multiple Targets for Therapy
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. HS Tissue and Blood Sample Extraction, Processing, and Sequencing Methods
2.2. HS Cell Line Growth, Maintenance, and RNA Preparation
2.3. RNA-Seq Analysis
2.4. Upstream Regulator Analysis
2.5. Drug Efficacy Studies
2.6. Cell Viability Assay
2.7. Combination Index (CI)
3. Results
3.1. HS Tumor Gene Expression Results
3.2. ROSALIND HS Cell Line Gene Expression Results
3.3. HS vs. HHS Differential Gene Expression
3.4. Transcriptome Comparison of HS Cases with PTPN11 Variant vs. Without PTPN11 Variant
3.5. Differential Expression of Immune Checkpoint Genes
3.6. Effect of AURK Inhibitors
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Inhibitory Molecule | |||||
---|---|---|---|---|---|
Alias | Gene Name | Average Log2 Expression | Average Log2 Fold Change | Significance (p-adj) | Compared to Control |
A2AR | ADORA2A | 10.87 | −1.84 | 1.78 × 10−3 | Down |
A2BR | ADORA2B | 9.25 | 0.711 | N.S. | |
PD-L1 | CD274 | 13.64 | 2.36 | 1.84 × 10−4 | Up |
PD-L2 | PDCD1LG2 | 12.61 | 2.39 | 2.62 × 10−4 | Up |
PD-1 | PDCD1 | 8.50 | 0.128 | N.S. | |
TIM3 | HAVCR2 | 8.73 | 0.145 | N.S. | |
VISTA | VSIR | 14.27 | −3.14 | 7.31 × 10−7 | Down |
LAG3 | LAG3 | 10.71 | 0.497 | N.S. | |
IDO | IDO1 | 14.08 | 0.646 | N.S. | |
CTLA-4 | CTLA4 | 10.55 | 0.264 | N.S. | |
BTLA | BTLA | 11.10 | −3.46 | 1.7 × 10−4 | Down |
B7-H4 | VTCN1 | 7.17 | −3.33 | 1.08 × 10−3 | Down |
B7-H3 | CD276 | 12.98 | 2.45 | 9.01 × 10−5 | Up |
AT9283 | BI847325 | |
---|---|---|
BD (IC50) | 285.7 nM | 31.4 nM |
DH82 (IC50) | 117.5 nM | 19.7 nM |
OD (IC50) | 269.1 nM | 23.8 nM |
Cmax | 488.2 nM | 500 nM (in mice) |
Molecular Targets | Aurora A/B JAK2/3 ABL FLT3 | Aurora C MEK 2 |
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Engleberg, A.I.; Yang, Y.-T.; Schall, P.Z.; Takada, M.; Thaiwong-Nebelung, T.; Evans, J.M.; Ostrander, E.A.; Yuzbasiyan-Gurkan, V. Transcriptome Analysis of Canine Histiocytic Sarcoma Tumors and Cell Lines Reveals Multiple Targets for Therapy. Cancers 2025, 17, 954. https://doi.org/10.3390/cancers17060954
Engleberg AI, Yang Y-T, Schall PZ, Takada M, Thaiwong-Nebelung T, Evans JM, Ostrander EA, Yuzbasiyan-Gurkan V. Transcriptome Analysis of Canine Histiocytic Sarcoma Tumors and Cell Lines Reveals Multiple Targets for Therapy. Cancers. 2025; 17(6):954. https://doi.org/10.3390/cancers17060954
Chicago/Turabian StyleEngleberg, Alexander I., Ya-Ting Yang, Peter Z. Schall, Marilia Takada, Tuddow Thaiwong-Nebelung, Jacquelyn M. Evans, Elaine A. Ostrander, and Vilma Yuzbasiyan-Gurkan. 2025. "Transcriptome Analysis of Canine Histiocytic Sarcoma Tumors and Cell Lines Reveals Multiple Targets for Therapy" Cancers 17, no. 6: 954. https://doi.org/10.3390/cancers17060954
APA StyleEngleberg, A. I., Yang, Y.-T., Schall, P. Z., Takada, M., Thaiwong-Nebelung, T., Evans, J. M., Ostrander, E. A., & Yuzbasiyan-Gurkan, V. (2025). Transcriptome Analysis of Canine Histiocytic Sarcoma Tumors and Cell Lines Reveals Multiple Targets for Therapy. Cancers, 17(6), 954. https://doi.org/10.3390/cancers17060954